Improving the quality of protein structure models by selecting from alignment alternatives

Background  

In the area of protein structure prediction, recently a lot of effort has gone into the development of Model Quality Assessment Programs (MQAPs). MQAPs distinguish high quality protein structure models from inferior models. Here, we propose a new method to use an MQAP to improve the quality of models. With a given target sequence and template structure, we construct a number of different alignments and corresponding models for the sequence. The quality of these models is scored with an MQAP and used to choose the most promising model. An SVM-based selection scheme is suggested for combining MQAP partial potentials, in order to optimize for improved model selection.     

Environmental and socioeconomic drivers of woody vegetation recovery in a human‐modified landscape in the Rio Grande basin (Colombian Andes)

In the tropics, some agricultural lands are abandoned for economic or technical reasons, leading to the recovery of woody vegetation. Our research aimed to identify the main drivers of spontaneous recovery of vegetation in a basin located in the Colombian Andes. This was done by combining spatially explicit environmental and socioeconomic variables at landscape (e.g. distances to human settlements, to roads, and to forests and mean annual precipitation) and local scales (e.g. depth of the organic layer, soil bulk density, and canopy openness). These variables were measured in 28 temporal plots of 500 m² each, established in land cover transitions that showed the recovery of woody vegetation. The recovered woody vegetation between 1986 and 2012 exhibited a gregarious spatial pattern at the landscape scale. Ordination analysis showed distinct floristic composition among transitions and remnant forests, and species associated to each one through an indicator species analysis. Multivariate analyses revealed the relationship between the transitions and variables at both scales. Woody vegetation recovery occurred near remnant forests and far from human settlements at the landscape scale. The soil conditions (content and depth of the organic horizon and bulk density) were the main drivers at the local scale. Our findings also highlight the necessity to define different restoration approaches such as incorporation of sites where socioeconomic and environmental conditions favor the spontaneous recovery of vegetation into the existing network of protected areas in the region, and to implement active restoration projects in perturbed sites to accelerate the recovery process of Andean forests.     

A search for endogenous modulators of the GABA receptor in different regions of the rat CNS

The possible existence of endogenous substances other than γ-aminobutyric acid (GABA), that can also bind to rat brain GABA receptors, has been investigated in synaptic membranes derived from whole rat brain, or from cerebral cortex; as well as in isolated synaptic vesicles obtained from cerebral cortex, striatum, hypothalamus, cerebellum and spinal cord and in the superfusion fluid of electrically stimulated brain cortex slices, where a GABA-like substance is released by a calcium-dependent process. The detector used to study the presence of such presumed non-GABA endogenous ligands, were frozen and thawed rat brain synaptic membranes, that had been treated with 0.05% Triton X-100 and thoroughly washed. With this highly sensitive preparation, at least 5 pmol of GABA/ml could be detected. The extracts of the different preparations where these hypothetical ligands were looked for, were analyzed by means of gel filtration on Sephadez G-10, paper chromatography and high voltage electrophoresis. In a very great number of experiments performed, the only endogenous ligand detected was GABA itself.The possible influence of a number of peptides on binding of GABA to its receptor, was also looked for. No significant effect was found for substance P, neurotensin, cholecystokinin octapeptide sulfated, somatostatin, thyrotropin releasing hormone, luteinizing hormone releasing hormone, methionine enkephalin (all 10^?5 M), angiotensin II (10^?4 M), ACTH (3 × 10^?7M), poly-l-lysine (30 μg/ml) or poly-l-glutamate (30 μg/ml).     

International cooperation in salmon fisheries and a comparative law perspective on the salmon and ocean ranching industry

Abstract

The salmon industry has steadily developed during the last two decades, leading to an increasing awareness about the legal problems that need to be solved. Both production in ocean ranching and in captivity have prompted the enactment of important rules of international and domestic law. While international law has provided for a basic regulatory framework, embodied in the United Nations Convention on the Law of the Sea and a number of regional and bilateral treaties, domestic law has concentrated on the specific technical issues that relate to conservation, fishing rights, and organization of the industry generally.

The article discusses the aggregate of legal rules applicable to salmon production, including the comparative law perspective emerging from the national legislations of the main producers in the world. Various legal and economic models are identified and their incidence on the industry is examined in light of actual experiences. The rules of international law in the field are becoming consolidated, and domestic legislation is contributing new insights into the matter while, in addition, exercising a strong influence in the formation of customary law.     

A Cytoplasmic New Catalytic Subunit of Calcineurin in Trypanosoma cruzi and Its Molecular and Functional Characterization

Parasitological cure for Chagas disease is considered extremely difficult to achieve because of the lack of effective chemotherapeutic agents against Trypanosoma cruzi at different stages of infection. There are currently only two drugs available. These have several limitations and can produce serious side effects. Thus, new chemotherapeutic targets are much sought after. Among T. cruzi components involved in key processes such as parasite proliferation and host cell invasion, Ca²⁺-dependent molecules play an important role. Calcineurin (CaN) is one such molecule. In this study, we cloned a new isoform of the gene coding for CL strain catalytic subunit CaNA (TcCaNA2) and characterized it molecularly and functionally. There is one copy of the TcCaNA2 gene per haploid genome. It is constitutively transcribed in all T. cruzi developmental forms and is localized predominantly in the cytosol. In the parasite, TcCaNA2 is associated with CaNB. The recombinant protein TcCaNA2 has phosphatase activity that is enhanced by Mn²⁺/Ni²⁺. The participation of TcCaNA2 in target cell invasion by metacyclic trypomastigotes was also demonstrated. Metacyclic forms with reduced TcCaNA2 expression following treatment with morpholino antisense oligonucleotides targeted to TcCaNA2 invaded HeLa cells at a lower rate than control parasites treated with morpholino sense oligonucleotides. Similarly, the decreased expression of TcCaNA2 following treatment with antisense morpholino oligonucleotides partially affected the replication of epimastigotes, although to a lesser extent than the decrease in expression following treatment with calcineurin inhibitors. Our findings suggest that the calcineurin activities of TcCaNA2/CaNB and TcCaNA/CaNB, which have distinct cellular localizations (the cytoplasm and the nucleus, respectively), may play a critical role at different stages of T. cruzi development, the former in host cell invasion and the latter in parasite multiplication.     

Effects of anisomycin on brain protein synthesis and passive avoidance learning in newborn chicks

The effects of anisomycin (ANM) on newborn chicks have been studied with respect to brain protein synthesis, growth, EEG, toxicity, and several passive avoidance learning tasks. It was found that intracerebral ANM (80 nmol) gave a maximum inhibition of brain protein synthesis of 30%, while a combination of subcutaneous (10 μmol; 53 mg/kg) plus intracerebral (80 nmol; 21 μg) ANM, inhibited by 91% in the first 2 hr and by 75% in the subsequent 2 hr period. Cycloheximide (CXM) also in combined injections at the same doses as ANM, inhibited by 97% in the 4 hr that followed injection. However, all the CXM-injected chicks were dead by 18 hr, while the lethality of ANM did not differ from that of saline. ANM also did not affect EEG measured at 1, 3, 5, or 24 hr following the subcutaneous plus intracerebral injections, nor did ANM affect body or brain growth curves or brain protein accretion. In the learning experiments, animals were initially trained to peck at water-coated metal spheres (type A learning) or at water-imbibed birdseed (types B and C learning) in less than 1 sec, and were exposed to the same lures treated with the aversant methylanthranilate (MeA) one day later on one occasion (types A and B learning) or exposed twice (type C learning) and tested for learning retention one day later. Learning criterion was set as failure to peck at the lure during the first 20 sec of presentation. If ANM was injected 1 hr prior to MeA exposure, large and highly significant memory deficits were found during the retention test, as compared with saline injected controls. No effect of ANM was seen, however, if it was injected one day after learning, indicating that it did not interfere with retrieval mechanisms. ANM also decreased the external manifestations of fear or displeasure that chicks express during retention testing. Such manifestations have a high correlation with pecking suppression (r = 0.88, P < 0.001).